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Abstract- Point of care devices for the early diagnosis of that affect fluorescence intensity.
current relavant diseases of our society require novel Nowadays, fluorescence measurements are still performed
miniature and very effective devices. This contribution by fluorescence microscopes, which are bulky and expensive.
focuses on the description of behavioral models aimed to Future personalized medicine needs small and effective
develop custom readout Application-Specific Integrated diagnosis tools, including diagnosis by fluorescence. Quite
Circuits (ASICs) for the measurement of Fluorescence recently, the use of on-chip fluorescence and life-time
and Fluorescence life-time of target substances. The well detection with CMOS SPADs has been addressed by several
suited for the ASIC development Verilog-A behavioral research groups. In order to provide low cost, fully integrated
description language is used to describe the sensor, an solutions, fulfilling the necessary constraints in terms of
ultra sensitive Single Photon Avalanche Diode (SPAD) important parameters like power, significant progress is still
fabricated in a conventional CMOS process, and the needed. Having useful models for the SPAD sensor and the
fluorescence signal. fluorescence signal is of relevance for the development of the
new instrumentation and is also the aim of this contribution.
Index Terms-Verilog-A, behavioral, SPAD, Avalanche
Behavioral models allow the optimization of the design
photodiode, CMOS, fluorescence, molecular, diagnosis, life-time, choice at the simulation level, thus saving costs and time.
FLlM. Moreover, they allow to explore different architectures during
the development phase, which is of paramount importance to
I. INTRODUCTION
succeed in integration.
This contribution describes the key simulation models used,
Single-photon Avalanche Diodes (SPADs) are optical sensors which are based on the high level mixed-signal modeling
that can detect single photons. Due to the weakness of the language Verilog-A. Verilog-A allows the description of the
signal in biological experiments, SPADs offer great potential electrical and non-electrical parts of the system, allowing a
as highly sensitive biosensors. Moreover, SPAD devices can whole integration in a standard simulation environment
be fabricated in conventional CMOS processes, thus commonly used to develop integrated circuits. The description
exploiting the advantages of microelectronic technologies, of the electronics can be done at the maximum level (post
i.e., low cost, low power and high density of integration. layout) and the sensor and the incoming signal in Verilog-A.
Currently, CMOS SPADs are gaining interest in many single The sensor model can emulate the static and dynamic
photon detection applications. behaviors, and the main statistical effects of an SPAD. The
In this paper, we focus on the application of SPADs to the incoming signal is described as a set of photons reaching the
measurement of the Fluorescence life-time of excited sensor randomly in time, following an exponential decay. The
molecules. Fluorescence methods applied to medical sciences simulations reveal the characteristics required to track the
exploit the phenomenon of fluorescence to analyze fluorescence decay of different substances.
biomolecular details of living tissue. In recent years, they Section II overviews a general set-up for fluorescence
have become the key tool of many optical bioassays for the measurements and the SPAD detector. The Verilog-A models
instantaneous diagnosis and monitoring of a large number of for the SPAD and the fluorescence signal are presented in
diseases, including cancer, cardiorespiratory, Section III. In Section IV we describe an example of
neurodegenerative and immunological diseases. In particular, integration. Finally, the conclusions are given.
the measurement of the life-time has the advantage of being
insensitive to the fluorophore concentration and other factors
978-1-4673-9184-9/15/$31.00 ©lOIS IEEE
II. FLUORESCENCE MEASUREMENTS WITH SPADs v••
VB. + Vov
.!l-"
studies on this phenomenon in p-n junctions started in the A " "
0 E
1960s at the Shockley laboratory [I, 2], it was not until the $! 0
"
� Time /
time 0
time 1 1\ Figure 3. Cross section of one SPAD fabricated with the standard HV-AMS
0.35 J.lm CMOS technology. The deep p-tub in the edge of the p+/deep ntub
junction avoid premature breakdown.
1\
1\
III. BEHAVIORAL DESCRIPTIONS
1\
The behavior of an SPAD sensor is not described by
technology models. It is a p-n junction biased some Vav
above the breakdown voltage, thus working in the Geiger
time n
1\ mode. Several works have presented electrical models of
reconstructed histogram SPADs, including behavioral descriptions [9] representing
-
even the statistics of noise in these devices. For the purpose of
-
end
endmodule
Figure 4: Verilog-A code of an avalanche photodiode, considering a 180 Figure 5: Verilog-A code for the photon generation in a FUM TCSPC
nm process. experiment.
multi-exponential probability, depending on the target Figure 6 shows the result of the application of these models
substance to simulate. A table stores the time of arrival of the to the circuit presented in figure 2. An event is generated some
different events (photons) after firing a start signal (pulse of time after the reset signal, as expected. The anode of the
light). A section of the code randomly takes one of the SPAD goes from VSS after the reset, to the overvoltage at the
generated events and reduces the table size, eliminating such event time. The readout, consisting basically in a CMOS
event from the table. After the complete simulation the inverter, is going from VSS to VDD ( 1.8 V).
histogram must be reconstructed.
REFERENCES
--------'-
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Figure 6. Simulation in the Virtuoso Cadence design environment of the event
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IV. CONCLUSION
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This work has been partially supported by ACC 16 in
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